Time-dependent release mechanisms of drugs have been described in the literature for tablet, pellet and capsule formulation utilising a wide range of physicochemical and physicomechanical strategies. The common feature of all such formulations is that they are activated by contact with fluids following ingestion by the patient and the drug will be released at the predetermined time after administration. Only after the formulations come into contact with gastric fluids does the ‘clock’ start. Drug release subsequently takes place at a predicted time, although it will be appreciated that since the dosage unit will be travelling through the GI tract during the lag period, drug release will necessarily be at some unknown GI tract site. Using such formulation strategies, it will be possible to design delivery systems capable of releasing drugs according to chronotherapeutic principles and targeting release to the circadian rhythm of disease states (Stevens H N E, Chronopharmaceutical Drug Delivery. J Pharm Pharmac., 50 (s) 5 (1998)).
However, many of the formulations in the art rely on complex structures which can add to the cost of the manufacture of the drug and/or can be subject to malfunction leading to incorrect/inappropriate administration of the drug.
Delayed prolonged release formulations of verapamil, such as COVERA-HS® are known in the art. COVERA-HS® is a formulation designed to initiate release of verapamil 4-5 hours after ingestion. The delay in release is due to a layer between the active drug core and an outer semi-permeable membrane. However, the formulation is complex in its construction, requiring precision drilled holes in the outer membrane being formed.
Other tablet formulations have been described for pulsed release of verapamil, where a delay in release is effected by way of an outer hydroxypropylmethyl cellulose coating. There is the proposal to use such formulations in a chronotherapeutic manner.
Further verapamil formulations are described in U.S. Pat. No. 4,832,958, for example, although there is no teaching of formulations which show a delay in verapamil release.
It is amongst the objects of the present invention to obviate and/or mitigate at least one of the aforementioned disadvantages.
It is amongst the objects of the present invention to provide a formulation which may be easily and/or cheaply manufactured and which allows for an active agent to be administered in a prolonged manner, following a period of delay following administration.